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PD1/PD-L1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti-PD-L1 (Avelumab).

PD1/PD-L1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti-PD-L1 (Avelumab).
Author Information (click to view)

Gill AL, Green SA, Abdullah S, Le Saout C, Pittaluga S, Chen H, Turnier R, Lifson J, Godin S, Qin J, Sneller MC, Cuillerot JM, Sabzevari H, Lane HC, Catalfamo M,


Gill AL, Green SA, Abdullah S, Le Saout C, Pittaluga S, Chen H, Turnier R, Lifson J, Godin S, Qin J, Sneller MC, Cuillerot JM, Sabzevari H, Lane HC, Catalfamo M, (click to view)

Gill AL, Green SA, Abdullah S, Le Saout C, Pittaluga S, Chen H, Turnier R, Lifson J, Godin S, Qin J, Sneller MC, Cuillerot JM, Sabzevari H, Lane HC, Catalfamo M,

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AIDS (London, England) 2016 8 3()

Abstract
OBJECTIVE
The PD1/PD-L1 pathway plays a critical role in balancing immunity and host immunopathology. During chronic SIV/HIV infection there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control and its blockade may be a potential immunotherapeutic target.

METHODS
Lymph node biopsies from HIV infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV infected rhesus macaques (RMs).

RESULTS
PD-L1 expression was observed in cells with myloid/macrophage morphology (M) in HIV infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment.

CONCLUSIONS
Administration of anti-PD-L1 in chronic SIV infected RMs was well tolerated. Overall these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans.

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